The research outlined in this proposal is designed to provide a basic understanding of the role of persisting antigen in the regulation and maintenance of the immune response. In view of difficulties involved in analyzing interactions between persisting antigen, antibody and the various cell types involved in the immune response in vivo, an in vitro model system has been developed which is amenable to manipulation and yet accurately reproduces phenomena observed in vivo. The polymerized human serum albumin (HSA) antigen used in this system appears to persist in rabbits for at least a year, and in the absence of anti-HSA antibody, it is capable of inducing a secondary response. The data obtained to date suggest that circulating antibody levels are maintained and regulated in vivo by an antibody feedback system. The feedback system prevents persisting antigen from inducing antibody synthesis when circulating levels are high. However, when antibody levels fall below a critical level, the antigen is exposed and stimulates HSA reactive memory cells to synthesize antibody and to produce additional memory cells. The data to be obtained from the proposed research should provide a basis for critically evaluating this mechanism for maintaining circulating antibody levels and immunological memory. Persisting antigen appears to be associated with an accessory type cell and the proposed research is designed to characterize this cell and to determine the nature of this association. Experiments will be undertaken to determine the physical and biological properties of the retained antigen. Various forms of antigen will be compared to determine how modification of the antigen molecule affects antigen localization and persistence as well as induction and maintenance of the immune response. The prospect of being able to understand how the immune response is regulated and the prospect of then being able to control the immune resonse makes the study of these basic immunological phenomena both relevant and exciting.